This invention relates to a new class of chemical compounds which can be described generally as [1-oxo-2,3-hydrocarbylene-5-indanyloxy(and thio)]alkanoic acids, and the nontoxic pharmaceutically acceptable salts, esters and amides thereof. Further, this invention relates to methods for the preparation of such compounds, pharmaceutical compositions comprising such compounds and to methods of treatment comprising administering such compositions and compounds.
Pharmacological studies show that the instant compounds are effective diuretic and saluretic agents which can be used in the treatment of conditions associated with electrolyte and fluid retention. The instant compounds are also useful in the treatment of hypertension. In addition, these compounds are able to maintain the uric acid concentration in the body at pretreatment levels or to even effect a decrease in the uric acid concentration.
The compounds of this invention may be described more fully by the following general representation: ##SPC1##
Wherein A is oxygen or sulfur; X.sup.1 is selected from hydrogen, halogen such as fluoro, bromo, chloro, iodo and the like, and methyl, X.sup.2 is halogen, such as fluoro, chloro, bromo and iodo, methyl and trifluoromethyl, and taken together, the two X radicals may be joined to form a hydrocarbylene chain containing from 1 to 4 carbon atoms between their points of attachment, for example, trimethylene, tetramethylene, and 1,3-butadieneylene; Y is an alkylene or haloalkylene radical having a maximum of 4 carbon atoms as for example methylene, ethylene, propylidene, isopropylidene, isobutylidene, fluoromethylene and the like; R is hydrogen, or lower alkyl for example methyl, ethyl, propyl, isopropyl, butyl and the like; wherein the subscript t is either 1 or 0; and wherein Q represents a hydrocarbylene bridge containing, together with the carbon atoms of the indane nucleus to which they are attached, from 3 to 6 carbon atoms; and forming a hydrocarbylene ring which is either unsaturated, or saturated. The invention also includes the pharmaceutically acceptable salts, the lower alkyl ester, the amides and the derivatives where carboxy is replaced by 5-tetrazolyl.
For conceptual convenience the above described compounds of this invention may be considered as 2,3-hydrocarbylene derivatives of substituted 5-indanyloxyalkanoic acids.
When administered in therapeutic dosages, in conventional vehicles, the instant [1-oxo-2,3-hydrocarbylene-5-indanyloxy(and thio)] alkanoic acids effectively reduce the amount of sodium and chloride ions in the body, lower dangerous excesses of fluid levels and in general alleviate conditions usually associated with edema. In addition these compounds overcome a major problem associated with many of the presently available diuretics and saluretics. Many of the presently available diuretics and saluretics have a tendency upon administration to induce hyperuricemia which may precipitate uric acid or sodium urate or both in the body which may cause from mild to severe cases of gout. Thus the [1-oxo-2,3-hydrocarbylene-5-indanyloxy(and thio)]alkanoic acids of this invention provide an effective tool to treat those patients requiring diuretic and saluretic treatment without incurring the risk of inducing gout. Further the [1-oxo-2,5-hydrocarbylene-5-indanyloxy(and thio)]alkanoic acids of this invention are effective antihypertensive agents.
Thus it is an object of this invention to provide 2,3-hydrocarbylene indanes of the above description which offer diuretic, saluretic, uricosuric and antihypertensive activities.
It is also an object of this invention to provide processes for the preparation of such [1-oxo-2,3-hydrocarbylene-5-indanyloxy(and thio)]alkanoic acid indanes and to provide pharmaceutical compositions comprising a therapeutically effective amount of such compounds and to provide a method of treatment comprising administering such compounds and compositions.